Preparation of quaternary ammonium halides



Patented Oct. 19, l954 PREPARATION OF QUATERNARY AMMONIUM HALIDES Richard I). S-tayner, Berkeley, Calif., assignor to California Research Corporation, San Francisco, Calif., a corporation of Delaware No Drawing. Application June 29. 1953, Serial No. 364,938

4- Claims.

This invention relates to an improved process for I the production of germicidal quaternary ammonium halides. More particularly, the invention concerns an improvement in the production of highly germicidal quaternary ammonium halides resulting in improved yields of products which are non-acidic and substantially free of objectionable odors.

Germicidal quaternary ammonium halides are known to the art. They are conventionally prepared by condensing an hydrophobic organic halide with a tertiary-amine in the presence of water and, for the most part, may be illustrated by the formula:

in which at least one of the groups R1, R2, R3 and R4 is a hydrophobic organic group and the remaining groups are substituents of hydrocarbon structure, and the radical X is an halogen atom.

In the preparation of germicidal quaternary ammonium halides, the initial product of the condensation is ordinarily acidic. Since the germicidal activity of quaternary ammonium halides is generally best at alkaline pHs of 7.0 to 8.5, the condensation product must be further processed with alkaline materials to give the desired pH. When the condensation product is made alkaline, substantial amounts of tertiaryamine are liberated and it is immediately apparent that all of the tertiary-amine reactant has not been utilized in the formation of the desired. quaternary ammonium halide. These liberated tertiary-amines are essentially non-germicidal and act as contaminants. Furthermore, they are usually characterized by offensive odors which make the quaternary ammonium halide disagreeable to use.

It is, therefore, an object of this invention to provide an improved process for the production of germicidal quaternary ammonium halides.

It is a further object of the invention to produce highly germicidal quaternary ammonium halides in improved yields.

It is also an object of this invention to produce germicidal quaternary ammonium halides which are non-acidic.

A still further object of the invention is the production of germicidal quaternary ammonium halides which are substantially free of objectionable odors.

Other objects and advantages of the invention Ivill be apparent from the description which folows.

I have discovered that the production ofgermicidal quaternary ammonium halides by' condensing hydrophobic organic halides and tertiary-amines may be greatly improved and the foregoing objects attained by carrying out the condensation in the presence of water and 0.1 to 10% by weight of alkali metal bicarbonate based on the total organic halide and tertiaryamine.

Although the products of condensation reactions of organic halides and tertiary-amines are ordinarily acidic and have pHs as low as 1 to- 2, which adversely affect the germicidal activity, the products of the present process are neutral or slightly alkaline and have a'pH in the range of 7.0 to 8.5 and are germicidally effective without further treatment. Another advantage of the present process lies in the fact that the tertiary-amine reactant is substantially completely utilized, unlike conventional processes. The yields of quaternary ammonium halide are higher and the product is greatly improved both as to germicidal activity and odor.

Germicidal suitable for preparation by the process of this invention may be any of the Well-known class of,

quaternary ammonium germicides characterized by the formula:

X R2 R4 wherein at least one of the groups R1, R2, R3 and 7 R4 is an hydrophobic-lipophilic group of from 6 to 26 carbon atoms. Ordinarily, the entire cation portion of the molecule has a molecular weight of at least 165. The hydrophobic group may be long-chain alkyl, long-chain alkoxyalkyl, long-chain alkylarylmethyl, halogen-substituted long-chain alkylarylmethyl, long-chain alkylphenoxyalkyl, arylalkyl, etc. in nature. The remaining groups on the nitrogen atom other than the hydrophobic group are substituents of hydrocarbon structure usually containing a total of no more than 12. carbon atoms. The X in the above formula is any halogen atom.

Quaternary ammonium halides within the above description include the alkyl ammonium halides such as cetyltrimethyl ammonium bromide, alkylaryl ammonium halides such as octadecyldimethylbenzyl ammonium bromide and Other suitable types of quaterquaternary ammonium halides nary ammonium salts include those in which the molecule contains ether, amide or ester linkages such as octylphenoxyethoxyethyldimethylbenzyl ammonium chloride, N-(laurylcolaminoformylmethyl) -pyridinium chloride, etc. Still other particularly-suitable types of quaternary ammonium germicides are those in which the hydrophobic radical is characterized by substituted aromatic nucleus as in the case of lauryloxyphenyltrimethylammonium chloride, dodecylbenzyltrimethylammonium chloride, chlorinated dodecylbenzyltrimethylammonium chloride, nonylmethylbenzyldimethylbenzylammonium bromide, octadecylbenzyldiethylhydroxyethylammonium chloride, and the like. a

All of the above quaternaries are conventionally prepared by the condensation of the hydrophobic organic halide with a tertiary-amine having the desired substitutent groups. The condensation occurs readily in most cases when the reactants are mixed. In other cases the condensation may be accelerated if the reactants are heated together.

The most suitably adapted quaternary ammonium germicides of the above general types are the long-chain alkylbenzyltrimethylammonium halides, the long-chain alkylbenzyldimethylbenzylammonium halides, and the long-chain alkylbenzyldiethylhydroxyethylammonium halides in which the alkyl radical preferably contain from 8 to 18 carbon atoms. These latter quaternaries, prepared by the condensation of alkylbenzylhalides having an alkyl group of from 8 to 18 carbon atoms with tertiary-amines containing a total of no more than 12 carbon atoms, such as trimethylamine, triethylamine, dimethylbenzylamine, diethylethanolamine, triethanolamine, etc., are noted for their ease of preparation. However, the particular lability of the halogens of these nonylmethylbenzylbromides, dodecylbenzylchlorides, and the like, which renders them unusually suited for quaternization reactions, also apparently causes the formation of considerable amounts of tertiary-amine hydrohalide under conventional reaction conditions. Decomposition by hydrolysis, intermolecular condensation, etc. of the alkylbenzylhalide forms hydrogen halide which ties up the tertiary-amine as the hydrohalide. The presence of the tertiary-amine hydrohalide thus formed causes the product to have a low pH. Neutralization of the acidic product to bring its pH within the desired range liberates the tertiary-amine from its hydrohalide and thus contaminates the product and gives it an undesirable amine odor.

In accordance with the improved process of the present invention, as already stated, the organic halide is condensed with the tertiary-amine in the presence of water and an alkali metal bicarbonate which prevents the formation of the tertiary-amine hydrohalide.

The condensation of the organic halide and the tertiary-amine is facilitated by heating the reactants together. Temperatures in the range of 50 to 100 C. are particularly convenient. These temperatures include the reflux temperatures of various solvents such as methyl alcohol, ethyl alcohol and benzene which are often employed in the reaction for convenience of handling.

According to this invention, some water must be present during the reaction. For present purposes, it is preferred that water be present in amounts of to 50% by weight based on the total organic halide and tertiary-amine.

Any alkali metal bicarbonate may be employed in the present process. Examples of suitable bicarbonates include sodium bicarbonate, potassium bicarbonate, and lithium bicarbonate. Within the terms of this invention alkali metal bicarbonate also includes ammonium bicarbonate. Sodium bicarbonate is preferred, since it is readily available and economical to use. The bicarbonate is utilized in proportions of 0.1 to 10% and preferably 0.5 to 3% by weight based on the total organic halide and tertiary-amine present in the process.

The following additional examples are ofiered in further illustration of the invention. Unless otherwise specified, the proportions are given on a weight basis.

Example ,1

294 parts of dodecylbenzylchloride were introduced into a reaction vessel. A methanol solution of 59 parts of trimethylamine was added slowly with stirring and the combined mixture refluxed in the reaction vessel for one hour. The reaction was quantitative in yield, utilizing all of the dodecylbenzylchloride. The mixture was then cooled and removed from the reaction vessel. The cooled solution was diluted with an equal volume of water and. extracted three times with petroleum ether. The aqueous portion thus obtained was concentrated by evaporation and the product made up to a 10% by weight solution with distilled water.

The dodecylbenzyltrimethylquaternary ammonium chloride prepared above was acidic in nature (pH 1.5) and, therefore, undesirable as such for germicidal purposes. Sufficient sodium bicarbonate was added to bring the pH of the solution to approximately 7.0 to 8.0. This resulted in a strong fishy odor of trimethylamine which rendered the product very offensive to smell and disagreeable to use as a germicide.

Example 2 parts of dodecylbenzylchloride were placed in a glass reaction flask equipped with a reflux condenser. 25 parts of methanol were added. 5 parts of water and 1 part of sodium bicarbonate were then added, following which 24 parts of a 25% solution of trimethylamine in methanol were The above product consisting of dodecylbenzyl- V trimethylquaternary ammonium chloride in solution had a pH of 8.0. This pH did not change when the solution was heated on a steam plate for 8 hours. No objectionable odors of trimethylamine could be detected in the product.

The phenol coefiicient of the dodecylbenzyltrimethylquaternary ammonium chloride against Staphylococcus aureus was obtained by a method employing Letheen broth in the subculture to prevent bacteriostasis.

nesium salts, the phenol coeflicient was found to In distilled water the" phenol coeincient was 1250. In hard water con. taining 300 parts per million of calcium and mag-- be 710. In the presence of 10% horse serum, a phenol coeflicient of 100 was obtained.

By a comparison of the above examples, it will be seen that the products prepared in accordance with the improved process of the present invention have several very important advantages. Not only are they highly germicidal, but they are non-acidic and substantially free of objectionable odors as distinguished from products prepared according to conventional methods.

I claim:

1. In a process for producing germicidal quaternary ammonium halides by condensing an alkylbenzylhalide having an alkyl group of 8 to 18 carbon atoms and a tertiary-amine containing not more than 11 carbon atoms, the improvement which consists in carrying out the condensation in the presence of water and 0.1 to 10% by weight of alkali metal bicarbonate based on the total alkylbenzylhalide and tertiaryamine.

2. In a process for producing germicidal quaternary ammonium halides by condensing an ing not more than 11 carbon atoms, the improvement which consists in carrying out the condensation in the presence of water and 0.5 to 3% by weight of sodium bicarbonate based on the total alkylbenzylhalide and tertiary-amine.

3. In a process for producing germicidal quaternary ammonium chlorides by condensing an alkylbenzylchloride having an alkyl group of 8 to 18 carbon atoms and a tertiary-amine containing not more than 11 carbon atoms, the improvement which consists in carrying out the condensation in the presence of water and 0.5 to 3% by weight of sodium bicarbonate based on the total alkylbenzylchloride and tertiary-amine.

4. In a process for producing dodecylbenzyltrimethylquaternary ammonium chloride by condensing dodecylbenzylchl-oride and trimethylamine, the improvement which consists in carrying out the condensation in the presence of water and 0.5 to 3 by weight of sodium bicarbonate based on the total dodecylbenzylchloride and trimethylamine.

No references cited. 

1. IN A PROCESS FOR PRODUCING GERMICIDAL QUATERNARY AMMONIUM HALIDES BY CONDENSING AN ALKYLBENZYLHALIDE HAVING AN ALKYL GROUP OF 8 TO 18 CARBON ATOMS AND A TERTIARY-AMINE CONTAINING NOT MORE THAN 11 CARBON ATOMS, THE IMPROVEMENT WHICH CONSISTS IN CARRYING OUT THE CONDENSATION IN THE PRESENCE OF WATER AND 0.1 TO 10% BY WEIGHT OF ALKALI METAL BICARBONATE BASED ON THE TOTAL ALKYLBENZYLHIDE AND TERTIARYAMINE. 